TFAP2A Activates S100A2 to Mediate Glutamine Metabolism and Promote Lung Adenocarcinoma Metastasis

IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM
Tao Zeng, Wangsheng Ren, Hang Zeng, Dachun Wang, Xianyu Wu, Guo Xu
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引用次数: 0

Abstract

Background

Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article.

Methods

The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate.

Results

S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis.

Conclusion

In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.

Abstract Image

TFAP2A激活S100A2介导谷氨酰胺代谢并促进肺腺癌转移
背景:肺腺癌(LUAD)是一种代谢异常的致命疾病。S100 蛋白家族成员 S100 钙结合蛋白 A2(S100A2)的失调与多种癌症的发生有关。然而,S100A2对LUAD发生和转移的影响尚未见报道。本文研究了S100A2对LUAD细胞转移的功能机制:方法:通过生物信息学和 qRT-PCR 方法分别分析了 TFAP2A 和 S100A2 在 LUAD 组织和细胞中的表达。对 S100A2 进行了富集通路分析。生物信息学分析确定了TFAP2A和S100A2之间的结合关系,并通过双荧光素酶和染色质免疫共沉淀实验验证了它们之间的相互作用。使用细胞计数试剂盒-8(CCK-8)测定细胞活力。采用转孔试验分析细胞的侵袭和迁移。免疫荧光法检测波形蛋白和 E-cadherin 的表达,Western 印迹法检测 MMP-2、MMP-9、GLS 和 GLUD1 的表达。试剂盒检测了NADPH/NADP比率、谷胱甘肽(GSH)/二硫化谷胱甘肽(GSSG)水平以及谷氨酰胺、α-KG和谷氨酸的含量:结果:S100A2在LUAD组织和细胞中上调,S100A2介导谷氨酰胺代谢诱导LUAD转移。此外,还发现了S100A2上游的转录调节因子TFAP2A,TFAP2A在LUAD中表达上调,表明TFAP2A促进了S100A2的表达。拯救实验发现,S100A2的上调可以逆转沉默TFAP2A对谷氨酰胺代谢和细胞转移的抑制作用:总之,通过调节谷氨酰胺代谢,TFAP2A/S100A2轴促进了LUAD的转移。结论:通过调节谷氨酰胺代谢,TFAP2A/S100A2轴促进了LUAD的转移,这表明靶向S100A2可能有利于LUAD的治疗。
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来源期刊
Clinical Respiratory Journal
Clinical Respiratory Journal 医学-呼吸系统
CiteScore
3.70
自引率
0.00%
发文量
104
审稿时长
>12 weeks
期刊介绍: Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)
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